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Patrick Schwab

Publications and source records attributed to Patrick Schwab.

At least 19 recordsLinked to original sources
arXiv2026

ViroGym: Realistic Large-Scale Benchmarks for Evaluating Viral Proteins

Protein language models (pLMs) have shown strong potential for zero-shot prediction of missense variant effects, yet systematic benchmarking on viral proteins remains limited, a critical gap given the need for proactive tools that can anticipate emerging mutations ahead of experimental validation. Here we introduce ViroGym, a comprehensive benchmark evaluating pLMs across three tasks: 79 deep mutational scanning (DMS) assays covering eukaryotic viruses with 552,065 mutated sequences across 7 phenotypic readouts, 21 influenza neutralisation tasks, and a real-world pandemic prediction task for SARS-CoV-2. We benchmark well-established pLMs on fitness landscapes, antigenic diversity, and pandemic forecasting, and find that the ProGen2 family consistently achieves the strongest performance across all three tasks. Crucially, DMS and neutralisation performance reliably identifies models that generalise to real-world emergence, even though the mutation sets they surface barely overlap, revealing that complementary in vitro benchmarks capture the evolutionary constraints needed for real-world mutation forecasting.

q-bio.QM↗
arXiv2025

Theoretical Guarantees for Causal Discovery on Large Random Graphs

We investigate theoretical guarantees for the false-negative rate (FNR) -- the fraction of true causal edges whose orientation is not recovered, under single-variable random interventions and an $\epsilon$-interventional faithfulness assumption that accommodates latent confounding. For sparse Erd\H{o}s--R\'enyi directed acyclic graphs, where the edge probability scales as $p_e = \Theta(1/d)$, we show that the FNR concentrates around its mean at rate $O(\frac{\log d}{\sqrt d})$, implying that large deviations above the expected error become exponentially unlikely as dimensionality increases. This concentration ensures that derived upper bounds hold with high probability in large-scale settings. Extending the analysis to generalized Barab\'asi--Albert graphs reveals an even stronger phenomenon: when the degree exponent satisfies $\gamma > 3$, the deviation width scales as $O(d^{\beta - \frac{1}{2}})$ with $\beta = 1/(\gamma - 1) < \frac{1}{2}$, and hence vanishes in the limit. This demonstrates that realistic scale-free topologies intrinsically regularize causal discovery, reducing variability in orientation error. These finite-dimension results provide the first dimension-adaptive, faithfulness-robust guarantees for causal structure recovery, and challenge the intuition that high dimensionality and network heterogeneity necessarily hinder accurate discovery. Our simulation results corroborate these theoretical predictions, showing that the FNR indeed concentrates and often vanishes in practice as dimensionality grows.

cs.LG↗
arXiv2025

Sensing Cardiac Health Across Scenarios and Devices: A Multi-Modal Foundation Model Pretrained on Heterogeneous Data from 1.7 Million Individuals

Cardiac biosignals, such as electrocardiograms (ECG) and photoplethysmograms (PPG), are of paramount importance for the diagnosis, prevention, and management of cardiovascular diseases, and have been extensively used in a variety of clinical tasks. Conventional deep learning approaches for analyzing these signals typically rely on homogeneous datasets and static bespoke models, limiting their robustness and generalizability across diverse clinical settings and acquisition protocols. In this study, we present a cardiac sensing foundation model (CSFM) that leverages advanced transformer architectures and a generative, masked pretraining strategy to learn unified representations from vast, heterogeneous health records. Our model is pretrained on an innovative multi-modal integration of data from multiple large-scale datasets (including MIMIC-III-WDB, MIMIC-IV-ECG, and CODE), comprising cardiac signals and the corresponding clinical or machine-generated text reports from approximately 1.7 million individuals. We demonstrate that the embeddings derived from our CSFM not only serve as effective feature extractors across diverse cardiac sensing scenarios, but also enable seamless transfer learning across varying input configurations and sensor modalities. Extensive evaluations across diagnostic tasks, demographic information recognition, vital sign measurement, clinical outcome prediction, and ECG question answering reveal that CSFM consistently outperforms traditional one-modal-one-task approaches. Notably, CSFM exhibits robust performance across multiple ECG lead configurations from standard 12-lead systems to single-lead setups, and in scenarios where only ECG, only PPG, or a combination thereof is available. These findings highlight the potential of CSFM as a versatile and scalable solution, for comprehensive cardiac monitoring.

cs.LG↗
arXiv2025

In-silico biological discovery with large perturbation models

Data generated in perturbation experiments link perturbations to the changes they elicit and therefore contain information relevant to numerous biological discovery tasks -- from understanding the relationships between biological entities to developing therapeutics. However, these data encompass diverse perturbations and readouts, and the complex dependence of experimental outcomes on their biological context makes it challenging to integrate insights across experiments. Here, we present the Large Perturbation Model (LPM), a deep-learning model that integrates multiple, heterogeneous perturbation experiments by representing perturbation, readout, and context as disentangled dimensions. LPM outperforms existing methods across multiple biological discovery tasks, including in predicting post-perturbation transcriptomes of unseen experiments, identifying shared molecular mechanisms of action between chemical and genetic perturbations, and facilitating the inference of gene-gene interaction networks.

cs.LG↗
arXiv2025

Multi-megabase scale genome interpretation with genetic language models

Understanding how molecular changes caused by genetic variation drive disease risk is crucial for deciphering disease mechanisms. However, interpreting genome sequences is challenging because of the vast size of the human genome, and because its consequences manifest across a wide range of cells, tissues and scales -- spanning from molecular to whole organism level. Here, we present Phenformer, a multi-scale genetic language model that learns to generate mechanistic hypotheses as to how differences in genome sequence lead to disease-relevant changes in expression across cell types and tissues directly from DNA sequences of up to 88 million base pairs. Using whole genome sequencing data from more than 150 000 individuals, we show that Phenformer generates mechanistic hypotheses about disease-relevant cell and tissue types that match literature better than existing state-of-the-art methods, while using only sequence data. Furthermore, disease risk predictors enriched by Phenformer show improved prediction performance and generalisation to diverse populations. Accurate multi-megabase scale interpretation of whole genomes without additional experimental data enables both a deeper understanding of molecular mechanisms involved in disease and improved disease risk prediction at the level of individuals.

q-bio.GN↗
arXiv2024

Efficient Differentiable Discovery of Causal Order

In the algorithm Intersort, Chevalley et al. (2024) proposed a score-based method to discover the causal order of variables in a Directed Acyclic Graph (DAG) model, leveraging interventional data to outperform existing methods. However, as a score-based method over the permutahedron, Intersort is computationally expensive and non-differentiable, limiting its ability to be utilised in problems involving large-scale datasets, such as those in genomics and climate models, or to be integrated into end-to-end gradient-based learning frameworks. We address this limitation by reformulating Intersort using differentiable sorting and ranking techniques. Our approach enables scalable and differentiable optimization of causal orderings, allowing the continuous score function to be incorporated as a regularizer in downstream tasks. Empirical results demonstrate that causal discovery algorithms benefit significantly from regularizing on the causal order, underscoring the effectiveness of our method. Our work opens the door to efficiently incorporating regularization for causal order into the training of differentiable models and thereby addresses a long-standing limitation of purely associational supervised learning.

cs.LG↗
arXiv2024

Deriving Causal Order from Single-Variable Interventions: Guarantees & Algorithm

Targeted and uniform interventions to a system are crucial for unveiling causal relationships. While several methods have been developed to leverage interventional data for causal structure learning, their practical application in real-world scenarios often remains challenging. Recent benchmark studies have highlighted these difficulties, even when large numbers of single-variable intervention samples are available. In this work, we demonstrate, both theoretically and empirically, that such datasets contain a wealth of causal information that can be effectively extracted under realistic assumptions about the data distribution. More specifically, we introduce a novel variant of interventional faithfulness, which relies on comparisons between the marginal distributions of each variable across observational and interventional settings, and we introduce a score on causal orders. Under this assumption, we are able to prove strong theoretical guarantees on the optimum of our score that also hold for large-scale settings. To empirically verify our theory, we introduce Intersort, an algorithm designed to infer the causal order from datasets containing large numbers of single-variable interventions by approximately optimizing our score. Intersort outperforms baselines (GIES, DCDI, PC and EASE) on almost all simulated data settings replicating common benchmarks in the field. Our proposed novel approach to modeling interventional datasets thus offers a promising avenue for advancing causal inference, highlighting significant potential for further enhancements under realistic assumptions.

cs.LG↗
arXiv2024

Multi-omics Prediction from High-content Cellular Imaging with Deep Learning

High-content cellular imaging, transcriptomics, and proteomics data provide rich and complementary views on the molecular layers of biology that influence cellular states and function. However, the biological determinants through which changes in multi-omics measurements influence cellular morphology have not yet been systematically explored, and the degree to which cell imaging could potentially enable the prediction of multi-omics directly from cell imaging data is therefore currently unclear. Here, we address the question of whether it is possible to predict bulk multi-omics measurements directly from cell images using Image2Omics - a deep learning approach that predicts multi-omics in a cell population directly from high-content images of cells stained with multiplexed fluorescent dyes. We perform an experimental evaluation in gene-edited macrophages derived from human induced pluripotent stem cells (hiPSC) under multiple stimulation conditions and demonstrate that Image2Omics achieves significantly better performance in predicting transcriptomics and proteomics measurements directly from cell images than predictions based on the mean observed training set abundance. We observed significant predictability of abundances for 4927 (18.72%; 95% CI: 6.52%, 35.52%) and 3521 (13.38%; 95% CI: 4.10%, 32.21%) transcripts out of 26137 in M1 and M2-stimulated macrophages respectively and for 422 (8.46%; 95% CI: 0.58%, 25.83%) and 697 (13.98%; 95% CI: 2.41%, 32.83%) proteins out of 4986 in M1 and M2-stimulated macrophages respectively. Our results show that some transcript and protein abundances are predictable from cell imaging and that cell imaging may potentially, in some settings and depending on the mechanisms of interest and desired performance threshold, even be a scalable and resource-efficient substitute for multi-omics measurements.

q-bio.QM↗
arXiv2024

Sample Selection Bias in Machine Learning for Healthcare

While machine learning algorithms hold promise for personalised medicine, their clinical adoption remains limited, partly due to biases that can compromise the reliability of predictions. In this paper, we focus on sample selection bias (SSB), a specific type of bias where the study population is less representative of the target population, leading to biased and potentially harmful decisions. Despite being well-known in the literature, SSB remains scarcely studied in machine learning for healthcare. Moreover, the existing machine learning techniques try to correct the bias mostly by balancing distributions between the study and the target populations, which may result in a loss of predictive performance. To address these problems, our study illustrates the potential risks associated with SSB by examining SSB's impact on the performance of machine learning algorithms. Most importantly, we propose a new research direction for addressing SSB, based on the target population identification rather than the bias correction. Specifically, we propose two independent networks(T-Net) and a multitasking network (MT-Net) for addressing SSB, where one network/task identifies the target subpopulation which is representative of the study population and the second makes predictions for the identified subpopulation. Our empirical results with synthetic and semi-synthetic datasets highlight that SSB can lead to a large drop in the performance of an algorithm for the target population as compared with the study population, as well as a substantial difference in the performance for the target subpopulations that are representative of the selected and the non-selected patients from the study population. Furthermore, our proposed techniques demonstrate robustness across various settings, including different dataset sizes, event rates, and selection rates, outperforming the existing bias correction techniques.

cs.LG↗
arXiv2024

Federated Causal Discovery From Interventions

Causal discovery serves a pivotal role in mitigating model uncertainty through recovering the underlying causal mechanisms among variables. In many practical domains, such as healthcare, access to the data gathered by individual entities is limited, primarily for privacy and regulatory constraints. However, the majority of existing causal discovery methods require the data to be available in a centralized location. In response, researchers have introduced federated causal discovery. While previous federated methods consider distributed observational data, the integration of interventional data remains largely unexplored. We propose FedCDI, a federated framework for inferring causal structures from distributed data containing interventional samples. In line with the federated learning framework, FedCDI improves privacy by exchanging belief updates rather than raw samples. Additionally, it introduces a novel intervention-aware method for aggregating individual updates. We analyze scenarios with shared or disjoint intervened covariates, and mitigate the adverse effects of interventional data heterogeneity. The performance and scalability of FedCDI is rigorously tested across a variety of synthetic and real-world graphs.

cs.LG↗
arXiv2023

DiscoBAX: Discovery of Optimal Intervention Sets in Genomic Experiment Design

The discovery of therapeutics to treat genetically-driven pathologies relies on identifying genes involved in the underlying disease mechanisms. Existing approaches search over the billions of potential interventions to maximize the expected influence on the target phenotype. However, to reduce the risk of failure in future stages of trials, practical experiment design aims to find a set of interventions that maximally change a target phenotype via diverse mechanisms. We propose DiscoBAX, a sample-efficient method for maximizing the rate of significant discoveries per experiment while simultaneously probing for a wide range of diverse mechanisms during a genomic experiment campaign. We provide theoretical guarantees of approximate optimality under standard assumptions, and conduct a comprehensive experimental evaluation covering both synthetic as well as real-world experimental design tasks. DiscoBAX outperforms existing state-of-the-art methods for experimental design, selecting effective and diverse perturbations in biological systems.

q-bio.QM↗
arXiv2023

The CausalBench challenge: A machine learning contest for gene network inference from single-cell perturbation data

In drug discovery, mapping interactions between genes within cellular systems is a crucial early step. Such maps are not only foundational for understanding the molecular mechanisms underlying disease biology but also pivotal for formulating hypotheses about potential targets for new medicines. Recognizing the need to elevate the construction of these gene-gene interaction networks, especially from large-scale, real-world datasets of perturbed single cells, the CausalBench Challenge was initiated. This challenge aimed to inspire the machine learning community to enhance state-of-the-art methods, emphasizing better utilization of expansive genetic perturbation data. Using the framework provided by the CausalBench benchmark, participants were tasked with refining the current methodologies or proposing new ones. This report provides an analysis and summary of the methods submitted during the challenge to give a partial image of the state of the art at the time of the challenge. Notably, the winning solutions significantly improved performance compared to previous baselines, establishing a new state of the art for this critical task in biology and medicine.

cs.LG↗
arXiv2023

CausalBench: A Large-scale Benchmark for Network Inference from Single-cell Perturbation Data

Causal inference is a vital aspect of multiple scientific disciplines and is routinely applied to high-impact applications such as medicine. However, evaluating the performance of causal inference methods in real-world environments is challenging due to the need for observations under both interventional and control conditions. Traditional evaluations conducted on synthetic datasets do not reflect the performance in real-world systems. To address this, we introduce CausalBench, a benchmark suite for evaluating network inference methods on real-world interventional data from large-scale single-cell perturbation experiments. CausalBench incorporates biologically-motivated performance metrics, including new distribution-based interventional metrics. A systematic evaluation of state-of-the-art causal inference methods using our CausalBench suite highlights how poor scalability of current methods limits performance. Moreover, methods that use interventional information do not outperform those that only use observational data, contrary to what is observed on synthetic benchmarks. Thus, CausalBench opens new avenues in causal network inference research and provides a principled and reliable way to track progress in leveraging real-world interventional data.

cs.LG↗
arXiv2022

Federated Learning in Multi-Center Critical Care Research: A Systematic Case Study using the eICU Database

Federated learning (FL) has been proposed as a method to train a model on different units without exchanging data. This offers great opportunities in the healthcare sector, where large datasets are available but cannot be shared to ensure patient privacy. We systematically investigate the effectiveness of FL on the publicly available eICU dataset for predicting the survival of each ICU stay. We employ Federated Averaging as the main practical algorithm for FL and show how its performance changes by altering three key hyper-parameters, taking into account that clients can significantly vary in size. We find that in many settings, a large number of local training epochs improves the performance while at the same time reducing communication costs. Furthermore, we outline in which settings it is possible to have only a low number of hospitals participating in each federated update round. When many hospitals with low patient counts are involved, the effect of overfitting can be avoided by decreasing the batchsize. This study thus contributes toward identifying suitable settings for running distributed algorithms such as FL on clinical datasets.

cs.LG↗
arXiv2022

Learning Neural Causal Models with Active Interventions

Discovering causal structures from data is a challenging inference problem of fundamental importance in all areas of science. The appealing properties of neural networks have recently led to a surge of interest in differentiable neural network-based methods for learning causal structures from data. So far, differentiable causal discovery has focused on static datasets of observational or fixed interventional origin. In this work, we introduce an active intervention targeting (AIT) method which enables a quick identification of the underlying causal structure of the data-generating process. Our method significantly reduces the required number of interactions compared with random intervention targeting and is applicable for both discrete and continuous optimization formulations of learning the underlying directed acyclic graph (DAG) from data. We examine the proposed method across multiple frameworks in a wide range of settings and demonstrate superior performance on multiple benchmarks from simulated to real-world data.

stat.ML↗
arXiv2022

Conditional Generation of Medical Time Series for Extrapolation to Underrepresented Populations

The widespread adoption of electronic health records (EHRs) and subsequent increased availability of longitudinal healthcare data has led to significant advances in our understanding of health and disease with direct and immediate impact on the development of new diagnostics and therapeutic treatment options. However, access to EHRs is often restricted due to their perceived sensitive nature and associated legal concerns, and the cohorts therein typically are those seen at a specific hospital or network of hospitals and therefore not representative of the wider population of patients. Here, we present HealthGen, a new approach for the conditional generation of synthetic EHRs that maintains an accurate representation of real patient characteristics, temporal information and missingness patterns. We demonstrate experimentally that HealthGen generates synthetic cohorts that are significantly more faithful to real patient EHRs than the current state-of-the-art, and that augmenting real data sets with conditionally generated cohorts of underrepresented subpopulations of patients can significantly enhance the generalisability of models derived from these data sets to different patient populations. Synthetic conditionally generated EHRs could help increase the accessibility of longitudinal healthcare data sets and improve the generalisability of inferences made from these data sets to underrepresented populations.

cs.LG↗
arXiv2021

GeneDisco: A Benchmark for Experimental Design in Drug Discovery

In vitro cellular experimentation with genetic interventions, using for example CRISPR technologies, is an essential step in early-stage drug discovery and target validation that serves to assess initial hypotheses about causal associations between biological mechanisms and disease pathologies. With billions of potential hypotheses to test, the experimental design space for in vitro genetic experiments is extremely vast, and the available experimental capacity - even at the largest research institutions in the world - pales in relation to the size of this biological hypothesis space. Machine learning methods, such as active and reinforcement learning, could aid in optimally exploring the vast biological space by integrating prior knowledge from various information sources as well as extrapolating to yet unexplored areas of the experimental design space based on available data. However, there exist no standardised benchmarks and data sets for this challenging task and little research has been conducted in this area to date. Here, we introduce GeneDisco, a benchmark suite for evaluating active learning algorithms for experimental design in drug discovery. GeneDisco contains a curated set of multiple publicly available experimental data sets as well as open-source implementations of state-of-the-art active learning policies for experimental design and exploration.

cs.LG↗